WO2017171988A2 - Étiquettes optiques à semi-conducteur à oxyde de métal complémentaire (cmos) actives à échelle micronique - Google Patents

Étiquettes optiques à semi-conducteur à oxyde de métal complémentaire (cmos) actives à échelle micronique Download PDF

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Publication number
WO2017171988A2
WO2017171988A2 PCT/US2017/014569 US2017014569W WO2017171988A2 WO 2017171988 A2 WO2017171988 A2 WO 2017171988A2 US 2017014569 W US2017014569 W US 2017014569W WO 2017171988 A2 WO2017171988 A2 WO 2017171988A2
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WIPO (PCT)
Prior art keywords
signals
integrated circuit
optical
cell
cells
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PCT/US2017/014569
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English (en)
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WO2017171988A3 (fr
Inventor
Kenneth Shepard
Girish RAMAKRISHNAN
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The Trustees Of Columbia University In The City Of New York
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Publication of WO2017171988A2 publication Critical patent/WO2017171988A2/fr
Publication of WO2017171988A3 publication Critical patent/WO2017171988A3/fr
Priority to US16/041,373 priority Critical patent/US11112360B2/en
Priority to US17/360,667 priority patent/US20210404963A1/en

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0002—Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network
    • A61B5/0031—Implanted circuitry
    • G—PHYSICS
    • G02—OPTICS
    • G02F—OPTICAL DEVICES OR ARRANGEMENTS FOR THE CONTROL OF LIGHT BY MODIFICATION OF THE OPTICAL PROPERTIES OF THE MEDIA OF THE ELEMENTS INVOLVED THEREIN; NON-LINEAR OPTICS; FREQUENCY-CHANGING OF LIGHT; OPTICAL LOGIC ELEMENTS; OPTICAL ANALOGUE/DIGITAL CONVERTERS
    • G02F1/00—Devices or arrangements for the control of the intensity, colour, phase, polarisation or direction of light arriving from an independent light source, e.g. switching, gating or modulating; Non-linear optics
    • G02F1/01—Devices or arrangements for the control of the intensity, colour, phase, polarisation or direction of light arriving from an independent light source, e.g. switching, gating or modulating; Non-linear optics for the control of the intensity, phase, polarisation or colour 
    • G02F1/015—Devices or arrangements for the control of the intensity, colour, phase, polarisation or direction of light arriving from an independent light source, e.g. switching, gating or modulating; Non-linear optics for the control of the intensity, phase, polarisation or colour  based on semiconductor elements having potential barriers, e.g. having a PN or PIN junction
    • G02F1/025—Devices or arrangements for the control of the intensity, colour, phase, polarisation or direction of light arriving from an independent light source, e.g. switching, gating or modulating; Non-linear optics for the control of the intensity, phase, polarisation or colour  based on semiconductor elements having potential barriers, e.g. having a PN or PIN junction in an optical waveguide structure
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
    • H01L31/00—Semiconductor devices sensitive to infrared radiation, light, electromagnetic radiation of shorter wavelength or corpuscular radiation and specially adapted either for the conversion of the energy of such radiation into electrical energy or for the control of electrical energy by such radiation; Processes or apparatus specially adapted for the manufacture or treatment thereof or of parts thereof; Details thereof
    • H01L31/02—Details
    • H01L31/0232—Optical elements or arrangements associated with the device
    • H01L31/02327—Optical elements or arrangements associated with the device the optical elements being integrated or being directly associated to the device, e.g. back reflectors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2560/00—Constructional details of operational features of apparatus; Accessories for medical measuring apparatus
    • A61B2560/02—Operational features
    • A61B2560/0204—Operational features of power management
    • A61B2560/0214—Operational features of power management of power generation or supply
    • G—PHYSICS
    • G02—OPTICS
    • G02F—OPTICAL DEVICES OR ARRANGEMENTS FOR THE CONTROL OF LIGHT BY MODIFICATION OF THE OPTICAL PROPERTIES OF THE MEDIA OF THE ELEMENTS INVOLVED THEREIN; NON-LINEAR OPTICS; FREQUENCY-CHANGING OF LIGHT; OPTICAL LOGIC ELEMENTS; OPTICAL ANALOGUE/DIGITAL CONVERTERS
    • G02F1/00—Devices or arrangements for the control of the intensity, colour, phase, polarisation or direction of light arriving from an independent light source, e.g. switching, gating or modulating; Non-linear optics
    • G02F1/01—Devices or arrangements for the control of the intensity, colour, phase, polarisation or direction of light arriving from an independent light source, e.g. switching, gating or modulating; Non-linear optics for the control of the intensity, phase, polarisation or colour 
    • G02F1/015—Devices or arrangements for the control of the intensity, colour, phase, polarisation or direction of light arriving from an independent light source, e.g. switching, gating or modulating; Non-linear optics for the control of the intensity, phase, polarisation or colour  based on semiconductor elements having potential barriers, e.g. having a PN or PIN junction
    • G02F1/0155—Devices or arrangements for the control of the intensity, colour, phase, polarisation or direction of light arriving from an independent light source, e.g. switching, gating or modulating; Non-linear optics for the control of the intensity, phase, polarisation or colour  based on semiconductor elements having potential barriers, e.g. having a PN or PIN junction modulating the optical absorption
    • G02F1/0157—Devices or arrangements for the control of the intensity, colour, phase, polarisation or direction of light arriving from an independent light source, e.g. switching, gating or modulating; Non-linear optics for the control of the intensity, phase, polarisation or colour  based on semiconductor elements having potential barriers, e.g. having a PN or PIN junction modulating the optical absorption using electro-absorption effects, e.g. Franz-Keldysh [FK] effect or quantum confined stark effect [QCSE]

Definitions

  • CMOS SEMICONDUCTOR
  • CMOS Complementary Metal- Oxide-Semiconductor
  • Implanted and injected integrated circuits can provide an array of functionalities in diverse fields such as sensing of biomedical signals, drug delivery in targeted tissues, cell stimulation and overall monitoring of signals.
  • the integrated circuit IC
  • the integrated circuit can be appropriately passivated and can operate as the entire implanted system.
  • characteristics including size, power delivery and communication can determine the efficacy and outcome of the desired application.
  • the IC size can affect the area and manner in which it can be implanted and injected.
  • millimeter-scale chips can be often implanted at regions of interest only through surgery.
  • chips can be invasive to the living system in which they are embedded and can cause adverse effects to surrounding tissue.
  • millimiter-scale chips due to their large size, are not suitable for long-term sensing in the hosting tissue in order to obtain and measure characteristic signals related to intracellular or extracellular activity. Indeed, such chips are not capable of diffusing through tissue and perform their functions on more localized length scales.
  • power delivery to implanted chips can be performed wirelessly.
  • Certain wireless power configurations can involve coupling to electromagnetic or mechanical waves. Electromagnetic coupling at long wavelengths, such as in the radio frequency spectrum, can be performed using millimeter-scale antennas or the like for efficient energy capture. However, introducing additional hardware can increase the scaling of the IC chip. Alternatively, near-field power transfer can be performed between an implanted IC chip. However, such configurations can require that the IC chip is proximate to an external transceiver. In addition, energy harvesting from ultrasound can also be performed in implantable chips. Ultrasound can have a lower wavelength, and thus can operate with smaller antennas, such as, for example, transducers. However, the scalability of ultrasound to a few micron- ( ⁇ -) scale chips can be difficult, for example when utilizing high ultrasound frequencies that can have difficulty penetrating tissue.
  • the integrated circuit can include an energy harvester e.g., energy harvesting circuitry that is capable of collecting light/energy from an optical source. Using the harvested energy, the integrated circuit can power the existing circuitry and also provide optical signals for transmission.
  • an energy harvester can include one or more photovoltaic cells. The integration of energy harvesting circuitry directly on the chip helps to improve the scale of the integrated circuit and ensures near perpetual operation by using ambient energy sources.
  • the integrated circuit can include a sensor e.g., sensing circuitry coupled to the energy harvester to be powered by the collected energy and configured to measure one or more electrical or elecreochemical signals associated with the one or more cells or tissues.
  • the integrated circuit can include at least one optical modulator configured to transmit the one or more electrical or electrochemical signals as one or more optical signals.
  • the sensing circuitry and optical modulator can be coupled to the energy harvester allowing them to be powered by the harvested energy and modulate the optical signal that is subsequently transmitted.
  • the optical modulator can be post- processed on the IC chip, thus providing for transmitting electrical signals as optical signals that can be captured by a variety of imaging tools including cameras mounted on epi-fluorescent microscopes.
  • the implantable IC chips can be fashioned with certain fabrication techniques to improve size by reducing thickness and can incorporate energy harvesting circuits.
  • a method for performing nondestructive sensing of a cell or a tissue - in vivo, or in culture using an IC chip is provided.
  • the integrated circuit is implanted into the cell by, for example, injection of the integrated circuit to the desired tissue.
  • the implanted IC chip can include an energy harvestor e.g., energy harvesting circuitry configured to collect light from an optical source such as a lamp and/or ambient light.
  • the implanted IC chip can include sensing circuitry coupled to the energy harvestor so as to be powered by the collected light and configured to measure one or more electrical or electrochemical signals associated with the cell.
  • the IC chip can include at least one optical modulator configured to receive the one or more electrical signals and generate one or more optical signals.
  • the method can include receiving, by the integrated circuit, light transmitted by the optical source using the energy harvestor that is capable of powering the integrated circuit.
  • modulating the one or more electrical signals with the transmitted light by the optical modulator to generate the one or more optical signals.
  • the method can further include transmitting the one or more optical signals, by the optical modulator.
  • the transmitted one or more optical signals can be subsequently detected by an image sensor that is configured to measure and display the one or more optical signals.
  • Fig. 1 illustrates an exemplary system for performing non-destructive sensing and imaging of a cell, in accordance with one or more embodiments.
  • Fig. 2A illustrates an exemplary side perspective view of the disclosed integrated circuit, in accordance with one or more embodiments.
  • Fig. 2B illustrates an exemplary top view including cross-sectional views of the disclosed integrated circuit, in accordance with one or more embodiments.
  • Figs. 3A-3J illustrate an exemplary etching fabrication process for producing the optical modulator of the disclosed integrated circuit, in accordance with one or more embodiments.
  • Figs. 4A-4J illustrate an exemplary lift-off process for producing the optical modulator of the disclosed integrated circuit, in accordance with one or more embodiments.
  • Figs. 5A-5G illustrate an exemplary thinning process for producing the CMOS of the disclosed integrated circuit, in accordance with one or more embodiments.
  • Fig. 6 illustrates an exemplary block diagram of a system for performing non- destructive sensing and imaging of a cell, in accordance with one or more embodiments.
  • Figs. 7A-7D illustrate exemplary circuit diagrams of energy harvesting circuitry of the disclosed integrated circuit, in accordance with one or more embodiments.
  • Figs. 8A-8E illustrate exemplary structures of energy harvesting circuitry of the disclosed integrated circuit in a CMOS process, in accordance with one or more embodiments.
  • Fig. 9 illustrates an exemplary circuit diagram of a relaxation oscillator of the disclosed integrated circuit, in accordance with one or more embodiments.
  • Fig. 10 illustrates an exemplary circuit diagram of the gate leakage resistance of Fig. 9, in accordance with one or more embodiments.
  • Fig. 11 illustrates an exemplary process flow chart for performing nondestructive sensing and imaging of a cell, in accordance with one or more embodiments.
  • the integrated circuit is implanted in the tissue of interest and can include an energy harvester e.g., energy harvesting circuitry that is capable of collecting light from an optical source in order to power the integrated circuit.
  • Visible light can provide advantages over certain conventional wireless power supply techniques for implanted IC chips, at least in part, because visible light has a wavelength ranging from 400nm to 700nm. Accordingly, the wavelength can be smaller than the size of a few-micron-scale chip, and thus interference or diffraction can be reduced or eliminated.
  • light can directly transfer energy to silicon, which can have a bandgap of 1.12eV, and thus the chip can be implemented without an explicit transducer. As a result, the size of the IC chip can be reduced.
  • such energy harvesting circuitry can include one or more photovoltaic cells, a photovoltaic transducer or any other suitable energy harvesting circuitry.
  • the integration of energy harvesting circuitry directly into the CMOS IC chip e.g., via front-end processing helps to improve the scale of the integrated circuit and ensures near perpetual operation by using ambient energy sources.
  • These optically powered ⁇ -scale chips with the integrated energy harvester can be coupled with sensing electronics and logic functionalities in order to perform localized electrophysiological measurements, act as intracellular probes and can perform certain optically triggered stimulations.
  • the implantable integrated circuit can include at least one optical modulator configured to transmit one or more electrical or electrochemical signals as one or more optical signals.
  • the optical modulator can be connected to the sensing electronics and energy harvester so as to be powered by the harvested energy and modulate the optical signal that is subsequently transmitted.
  • modulating the optical signal can be achieved by modulating the intenisty of the optical signal, the wavelength of the optical signal, both the inetnsity and wavelength or any other suitable combination.
  • the optical modulator can be post-processed on the IC chip, thus providing for transmitting electrical signals as optical signals that can be captured by a variety of imaging tools.
  • modulation of light can be accomplished by using various fluorescent materials post-processed on the IC chip, which can reduce the overall consumption of power and allow for prolonged operation of the IC chip.
  • the implantable IC chips of the disclosed subject matter can be smaller than ⁇ in each dimension and can utilize visible light to power the IC chip and scaled CMOS technology to design electronics. Furthermore, in some embodiments, the implantable IC chips of the present disclosed subject matter can be smaller than ⁇ in each dimension.
  • the thickness of the IC chip can be reduced to approximately ⁇ through wafer/chip-thinning processes including, for example, back-side grinding, deep-reactive ion etching (DRIE), a 65nm bulk process or any other suitable size reduction technique.
  • DRIE deep-reactive ion etching
  • fully fabricated IC chips can be collected in de-ionized water and can be injected to a cell and/or tissue of interest.
  • the physical circuit of the chip can include additional components including, a relaxation oscillator and a driver for driving the optical modulator.
  • the power consumption can be reduced or minimized with a measured operating power of approximately lOOpW and measured oscillator frequency to modulate the electro-optic modulator of approximately 1.2Hz.
  • changing the oscillation frequency such as for example, by making modifications in the front-end silicon fabrication, or, for example, by modifying the electro-optic modulator across instances can result to different operational characteristics of the IC circuit relating to the tissue of interest.
  • Fig. 1 illustrates an exemplary system 100 for performing non-destructive sensing and imaging of a cell.
  • the exemplary embodiment depicted in Fig. 1 shows the IC chip 106 implanted in a cell placed on a microscopic slide 104.
  • IC chip 106 can be placed in solution or can be introduced into cells, tissues (e.g., in vivo or in culture) or cell cultures by injection/microinjection, endocytosis, or any other suitable technique.
  • the integrated circuit can be coated with a biocompatible material allowing the cell and/or tissue to accept the implantation.
  • the integrated circuit can be implanted in the tissue by use of a micropipette from a dispersion or solution in a compatible solvent such as deionized (DI) water.
  • IC chip 106 can be injected into any place of interest, such as, for example, individual cells and/or tissues, cell cultures, water or any other suitable area of interest.
  • IC chip can be fabricated to have dimensions of approximately ⁇ ⁇ ⁇ ⁇ ⁇ in order to fascilitate placement of the IC chip and reduce interference and/or diffraction from visible light.
  • the cell implanted IC chip 106 can be observed, for imaging and measuring purposes, by placing microscopic slide 104 under microscope 102.
  • microscope 102 can be a laboratory epi- fluorescent microscope including, for example, CMOS and Charged-Coupled Device (CCD) cameras, a spectrometer, a light source or other suitable optical probe/sensor configured to detect optical signals.
  • CCD Charged-Coupled Device
  • Fig. 2 A illustrates a large scale, top view of a microscopic slide 104 including cell 210 and an example implant IC chip 106.
  • Fig. 2A shows a larger side perspective view of implanted IC chip 106.
  • IC chip 106 includes various layered regions including backside substrate 202, frontside substrate 204, optical modulator 206 and energy harvesting circuitry 208.
  • backside substrate 202 can be a carrier substrate including a p-type semiconductor substrate fabricated using CMOS bulk processes.
  • frontside substrate 204 can be any suitable silicon substrate mounted onto carrier backside substrate 202 and fabricated using CMOS bulk processes such as a 65nm bulk process.
  • the thickness of the IC chip can be reduced from 300 ⁇ thick to approximately ⁇ through various wafer/chip-thinning processes including, for example, back-side grinding and deep-reactive ion etching (DRIE), removing the backside silicon by backside mechanical grinding, chemical mechanical polishing (CMP), physical or chemical etching, controlled spalling or any suitable combination of thinning processes.
  • the ultra-thin chip can be transferred to a flexible or rigid substrate, either before the thinning procedure, after the thinning procedure, or during the thinning process.
  • Optical modulator 206 can be post-processed on the CMOS IC chip such that it is over backside substrate 202 and frontside substrate 204.
  • optical modulator 206 can be fabricated using different techniques that are discussed below in reference to Figs. 2B-4J.
  • Energy harvesting circuitry 208 can be integrated directly into the CMOS IC front-end processing during fabrication of backside substrate 202. Such circuitry can provide techniques for converting light falling on it into usable electrical energy. For example, light can directly transfer energy to silicon, including backside substrate 202 and frontside substrate 204 which can have a bandgap of 1.12eV, and thus the implant IC chip 106 can be implemented without additional hardware e.g., an explicit transducer, which can reduce its overall size.
  • Energy harvesting circuitry 208 can be any suitable circuitry that can collect energy from natural and/or manufactured ambient energy sources such as lamps, sound, ambient light and others and will be further discussed below in reference to Fig. 2B.
  • Fig. 2B illustrates an exemplary top view including cross-sectional views of the implant integrated circuit 106 previously illustrated in Fig. 2 A.
  • implant IC 106 includes optical modulator 206 and energy harvesting circuitry 208.
  • Optical modulator 206 is post-processed on the chip and is capable of modulating and transmitting an optical signal detectable by optical probes/sensors, such as microscopes and cameras.
  • optical modulator 206 is an electro- optical modulator processed on the chip that can consume close to zero electrical power by using, for example, fluorescence material to emit optical signals.
  • the IC chip 106 can be powered by light interacting with it and can transmit information by electrical modulation of an optical signal using quantum dot fluorescence.
  • the optical modulator 206 can be fabricated using a dielectric stack of quantum dots 308 disposed between a dielectric material 310, such as hafnia, zirconia, alumina, silicon dioxide, or any other suitable thin film dielectric in order to form a quantum-dot capacitor (QDcap).
  • the dielectric 310 is chosen according to a low extinction coefficient and a high dielectric constant in order to increase or maximize the optical modulation.
  • using the Stark effect to modulate fluorescence emission of quantum dots can provide upto 10% optical modulation depth at ⁇ 50fW of power consumption and can allow easy scalability of fabrication process to die-level or wafer-level processing.
  • IC chip 106 includes top electrode 306 that can be implemented as a thin film transparent conductor to optically discern the fluorescence signal.
  • the top electrode 308 of the capacitor can be formed using indium tin oxide (ITO) and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) or any suitable thin film conductor.
  • ITO can be utilized at least in part to allow depositing of thin films of well-controlled thicknesses.
  • implant IC chip 106 includes energy harvesting circuitry 206 that collects light used for powering the integrated circuit.
  • energy harvesting circuitry 206 includes one or more photovoltaic cells that are fabricated using backside substrate 202 e.g., p-substrate, deep N-well substrate 304 and p-well substrate 302 as will be discussed in Fig. 8.
  • Figs. 3A-3F illustrate an exemplary etching fabrication process for producing the optical modulator 206 integrated in IC chip 106.
  • Fig. 3 A shows bulk silicon chips after passivation removal and top metal layer exposed including a region of silicon CMOS substrate 402 and one or more regions 404 that includes a metal such as aluminum.
  • Fig. 3B shows the deposition of one or more electrodes 406 over aluminum regions 404.
  • electrodes 406 are fabricated using gold or any other suitable material and can be lithographically defined and placed to form the electrical contacts on the modulator.
  • Figs. 3C-3E show an example process for atomic layer deposition (ALD) of dielectric material 310 such as hafnia.
  • ALD atomic layer deposition
  • Fig. 3C shows the deposition of a first layer of hafnia 403 over substrate region 402 and aluminum regions 404 in order to form a hafnia-quantum dot-hafnia stack required for the quantum dot capacitor described in reference to Fig. 2B.
  • Fig. 3D shows the deposition of quantum dot layer 408.
  • quantum dot layer 408 includes collodial quantum dots being spin coated on the chip.
  • Fig. 3E shows the deposition of a second layer of hafnia 405.
  • photoresist material 410 is applied to a portion of the chip.
  • an etch mask can be defined with an opening over one of the regions 404 to etch out the stack using a dry/wet etch strategy
  • deposition of the photoresist material 410 can be achieved by a photoresist (PR) spin coat and patterning etch mask in order to protect the deposition of the quantum dot layer 408 and ensure the efficiency of the optical modulator.
  • Fig. 3G shows the hafnia-QD stack etch through the photoresist mask 410.
  • Fig. 3H shows the deposition mask for patterning of the top electrode 308 of the capacitor. The deposition of the top electrode 308 is shown in Fig. 31.
  • the top electrode 308 can be formed using indium tin oxide (ITO) 412 and a new mask can be lithographically defined for the ITO 412, and the ITO can be deposited by sputtering or by electron beam deposition and can be patterned using a lift-off based strategy.
  • Fig. 3 J shows the photoresist material 410 removal and ITO 412 patterning by lift-off.
  • optical modulator 206 can also be fabricated by a lift-off fabrication process as shown in Figs. 4A-4J.
  • Fig. 4 A shows bulk silicon chips after passivation removal and top metal layer exposed including a region of silicon CMOS substrate 402 and one or more regions 404 that includes a metal such as aluminum.
  • Fig. 4B shows the deposition of one or more electrodes 406 over aluminum regions 404.
  • electrodes 406 are fabricated using gold or any other suitable material and can be lithographically defined and placed to form the electrical contacts on the modulator.
  • photoresist material 410 is applied to a portion of the chip.
  • a window can be lithographically defined over one of the regions 404 to define the hafnia-QD -hafnia stack.
  • deposition of the photoresist material 410 is achieved by a photoresist (PR) spin coat and patterning etch mask.
  • PR photoresist
  • Figs. 4D-4F show a process for atomic layer deposition (ALD) of dielectric material 312 such as hafnia.
  • ALD atomic layer deposition
  • Fig. 4D shows the deposition of a first layer of hafnia 403 over photoresist material 410, a portion of substrate region 402 and single aluminum region 404.
  • Fig. 4E shows the deposition of quantum dot layer 408.
  • quantum dot layer 408 includes collodial quantum dots being spin coated on the chip.
  • Fig. 4F shows the deposition of a second layer of hafnia 405.
  • Fig. 4G shows the hafnia-quantum dot stack lift-off.
  • Fig. 4H shows the deposition mask for patterning of the top electrode 308 of the capacitor.
  • the deposition of the top electrode 308 is shown in Fig. 41.
  • the top electrode 308 can be formed using indium tin oxide (ITO) 412 and a new mask can be lithographically defined for the ITO 412, and the ITO can be deposited by sputtering or by electron beam deposition and can be patterned using a lift-off based strategy.
  • Fig. 4J shows the photoresist material 410 removal and ITO 412 patterning by lift-off.
  • ITO indium tin oxide
  • the implant IC chip 106 with the integrated optical modulator 206 can be rendered thin in order to allow for the nondestructive implantation in the tissue of interest.
  • the thinning can be one of the last fabrication procedures, at least in part, because of the handling difficulties associated with thin dies.
  • the implant IC chip 106 can be thinned earlier into the process.
  • the thinning can include a variety of processes including mechanical grinding, CMP, physical etching, chemical etching or a combination of any suitable thinning process.
  • Figs. 5A-5G illustrate an exemplary thinning process for producing one or more implant CMOS integrated circuits 106.
  • Fig. 5A shows bulk CMOS chip including the die backside substrate 202 after post-processing optical modulator 206.
  • anisotropic etching is performed in order to determine chip boundary demarcations that can be defined by forming vertical trenches 501 around the chip area, as shown in Fig. 5B.
  • anisotropic etching can be performed using a sequence of etch procedures, as the frontside of the CMOS chip can differ in material properties from the backside of the CMOS chip. Such process can fascilitate the chip release after fabrication.
  • the exemplary thinning process provides topside encapsulation that places biocompatible layer 504 and topside mounting CMOS substrate 502 onto carrier substrate 202.
  • biocompatible layer 504 can include parylene or any other suitable biocompatible material in order to allow for compatibility of implant IC chip 106 within the tissue of interest.
  • the frontside substrate can be passivated by a conformal parylene coating which can be deposited in room temperature. The coating can render the chip biocompatible to inhibit or prevent it from being attacked by any reagents.
  • Fig. 5D shows coarse chip-thinning using backside grinding in order to reduce the size and thickness of substrate 202.
  • Fig. 5E shows fine chip-thinning using deep reactive ion etching (DRIE) or any other suitable etching technique.
  • DRIE deep reactive ion etching
  • the backside etch can be performed by a sequence of mechanical grinding, mechanical smoothening and/or polishing and deep reactive ion etching (DRIE), which is a highly anisotropic etching scheme that can combine both physical milling and chemical etching.
  • the one or more implant CMOS integrated circuits 106 are separated using trenches 501.
  • Fig. 5F shows backside encapsulation using an additional biocompatible layer
  • implant CMOS integrated circuits 106 are released from a handle wafer by, for example, scooping them out or by centrifugation or any other suitable release mechanism.
  • the one or more implant CMOS integrated circuits 106 are collected in de-ionized water.
  • implant IC chip 106 can include additional sensing and processing circuitry and data transfer circuitry integrated within using one or more of the fabrication processes illustrated in Figs. 3A-5G.
  • Fig. 6 illustrates an exemplary block diagram of a system for performing non-destructive sensing and imaging of a cell.
  • the implant IC chip 106 can be illuminated from a light source included in microscope 102 and the optically modulated data signal by the optical modulator 206 can also be captured by the microscope 102. Specifically, implant IC chip 106 can be injected into a cell and placed on microscopic slide 104 under microscope 102.
  • implant IC chip 106 is exposed to a light source included into the optical excitation setup module 612 of microscope 102.
  • the light source can be a lamp, flash light, LED light or any other suitable light source integrated in microscope 102.
  • the energy harvesting network 208 of implant IC chip 106 collects the illuminated energy.
  • energy harvesting network can include one or more photovotaic cells 208 that can generate a DC voltage capable of powering the implant IC chip 106 including the relaxation oscillator 604 and any additional detection/sensing circuitry 602.
  • detection/sensing circuitry 602 can include electropphysiological probes, or any other suitable circuitry capable of detecting and obtaining a measurement signal relating to, for example, intracellular activity.
  • the detected signal is subsequently modulated through optical modulator 206.
  • the spectrum of the excitation light, illuminated by optical excitation setup module 612 of microscope 102 can be separated for powering both the implant IC chip 106 using energy harvesting circuitry 208 and for data transmission using optical modulator 206.
  • the implant IC chip 106 can allow for simultaneous observation and powering under microscope 102.
  • relaxation oscillator 604 is powered by energy harvesting circuitry 208 and can drive optical modulator 206 by adjusting the oscillation frequency of the transmitted optical signal.
  • Figs. 7A-7D illustrate exemplary circuit diagrams of energy harvesting circuitry 208 integrated in implant IC chip 106.
  • energy harvesting circuitry 208 can be integrated on-chip and include one or more photovoltaic cells capable of powering IC chip 106, as shown in reference to Fig. 2B.
  • the photovoltaic cells can be constructed using a network of diodes connected in different configurations.
  • Fig. 7A illustrates a photovoltaic cell constructed using a single photodiode 702.
  • Fig. 7B illustrates two photodiodes 702 connected in series that are capable of providing a higher voltage supply to implant IC chip 106.
  • Fig. 7C illustrates two photodiodes 702 connected in parallel that are capable of providing a lower output impedance when powering implant IC chip 106. Additionally, Fig. 7D illustrates a photodiode 702 connected in series to two photodiodes 702 connected in parallel. In some embodiments, any number and combination of photodiodes 702 and/or isolated SOI diodes can be used for constructing the photovoltaic cells of energy harvesting circuitry 208.
  • photodiodes 702 previously discussed in reference to Figs. 7A-D can be fabricated using available p-n junctions in the CMOS process, as shown in Figs. 8A- 8E.
  • photodiodes 702 can include substrate-well diodes, diffusion-well diodes, substrate-diffusion diodes, triple-well diodes, polysilicon diodes, isolated diode junctions available in an SOI process, or any other suitable diode.
  • Fig. 8A illustrates an exemplary photodiode 702 that can be used as photovoltaic cells in a CMOS process frontend according to the disclosed subject matter.
  • Fig. 8A shows a p-diffusion n-well diode fabricated using a p- type substrate.
  • Fig. 8B shows an n-diffusion p-well diode fabricated using a deep n- type substrate.
  • Fig. 8C shows a p-well deep n-well diode.
  • Fig 8D shows a p- diffusion n-well diode on an SOI substrate and
  • Fig. 8E shows n-diffusion p-well diode on an SOI substrate.
  • SOI isolated diodes can be utilized at least because of the absence of a leaky parasitic substrate diode.
  • Fig. 9 illustrates an exemplary circuit diagram of relaxation oscillator 604 including comparator 902 logic NOT gates 908, resistor 906 and capacitor 904 forming a positive feedback loop that allows for the circuit too oscillate automatically.
  • the low-power relaxation oscillator 604 can be used to drive the optical modulator 208 by adjusting and setting an oscillation frequency.
  • a gate-leakage resistor 1000 can be used to implement the leakage current that defines oscillation frequency.
  • the gate-leakage resistor 1000 includes a p-channel MOSFET transistor 1004 connected to an N-channel MOSFET transistor 1002 that can achieve a large time constant using a small area constraint and provide a symmetric rise and fall time for the relaxation oscillator 604 and a duty cycle close to 50%.
  • the long time constant and low oscillation frequency can allow the usage of a reasonably long exposure time to image the implant IC chip 106.
  • Fig. 11 illustrates an exemplary process flow chart for performing nondestructive sensing and imaging of a cell.
  • implant IC chip 106 is introduced to a tissue of interest e.g., a cell.
  • one or more implant IC chips 106 can be introduced to different cells by injection/microinjection and/or tosis.
  • implant IC chip 106 is illuminated by a light source in order to harvest energy using energy harvesting circuitry 208 and produce DC voltage.
  • the light source can be integrated into microscope 102.
  • the produced DC voltage subsequently powers optical oscillator 206 and detection/sensing circuitry 602 at 1106.
  • the measured signal by detection/sensing circuitry 602 is modulated by optical modulator 208 in order to transmit an optical signal.
  • the relaxation oscillator can adjust the oscillation frequency for optical modulator 208 and at 1112 the modulated optical signal is detected by an image sensor.
  • the image sensor can be integrated into microscope 102.
  • any operations described herein that form part of one or more embodiments of the disclosure can be useful machine operations.
  • one or more embodiments of the disclosure also relate to a device or an apparatus for performing these operations.
  • the apparatus can be specially constructed for specific required purposes, or it can be a general purpose computer selectively activated or configured by a computer program stored in the computer.
  • various general purpose machines can be used with computer programs written in accordance with the teachings herein, or it can be more convenient to construct a more specialized apparatus to perform the required operations.

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Abstract

Cette invention concerne des systèmes et des procédés pour effectuer une détection non destructrice d'une cellule ou d'un tissu, in vivo ou en culture. Les systèmes et procédés selon l'invention comprennent la fabrication et l'alimentation d'une ou plusieurs puces de circuit intégré (IC) implantables qui comprennent un réseau de cellules photovoltaïques (PV) pour la récupération d'énergie à partir d'une source d'énergie optique, un modulateur optique intégrant des condensateurs à boîtes quantiques (embouts à boîtes quantiques) pour un transfert de données optiques par modulation de fluorescence, et un circuit de détection. La puce de circuit intégré selon l'invention peut mesurer une épaisseur d'environ 10 μm, permettant l'injection dans de petites cellules et la diffusion à travers le tissu, elle est alimentée et imagée sous microscope et communique par modulation de fluorescence imagée sous microscope.
PCT/US2017/014569 2016-01-21 2017-01-23 Étiquettes optiques à semi-conducteur à oxyde de métal complémentaire (cmos) actives à échelle micronique WO2017171988A2 (fr)

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US17/360,667 US20210404963A1 (en) 2016-01-21 2021-06-28 Methods and systems utilizing optically-powered sensing integrated circuit(s) with optical information transfer

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US20190060663A1 (en) 2019-02-28

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